K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-propane dibromide] is a promising new reactivator of organophosphate- or organophosphonate-inhibited acetylcholinesterase (AChE) with low acute toxicity and broad spectrum efficacy. The aim of the present study was to compare the pharmacokinetics of both compounds. Male Wistar rats (body weight = 320 ± 10 g) were administered a single intramuscular dose of K027 (22.07 mg kg(-1)) and an equimolar dose of trimedoxime. Blood was collected at various time intervals until 180 min. Plasma samples were analyzed by reversed-phase HPLC with ultraviolet (UV) detection. The recovery of both oximes from the plasma was approximately 90% and a linear relationship (R(2) > 0.998) was observed between the peak areas and concentrations of calibrated standards in the range 1-100 µg ml(-1). Near-identical plasma profiles were obtained for both compounds. No differences were found in the mean ± SD values of C(max) (18.6 ± 2.5 vs 20.0 ± 6.3 µg ml(-1), P = 0.72) and AUC(0-180min) (2290 ± 304 vs 2269 ± 197 min µg ml(-1), P = 0.84). However, the percentage coefficient of variation of the first-order rate constant of absorption (k(a)) was 3-fold higher (P < 0.01) providing evidence for more erratic absorption of intramuscular trimedoxime as compared with K027. In conclusion, oxime K027 might have superior pK properties that may be translated in its faster absorption and subsequent tissue distribution.

• MeSH
• injekce intramuskulární MeSH
• krysa rodu rattus MeSH
• oximy krev   farmakokinetika   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny krev   farmakokinetika   MeSH
• reaktivátory cholinesterázy krev   farmakokinetika   MeSH
• spektrofotometrie ultrafialová metody   MeSH
• tkáňová distribuce MeSH
• trimedoxim krev   farmakokinetika   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Oxime K203 is a new compound designed to be used as an acetylcholinesterase reactivator for the treatment of intoxication following exposure to tabun and certain pesticides. After intramuscular administration of a therapeutic (23 mg/kg) dose, the time-course of plasma concentrations of K203 in rats was determined by HPLC. Maximum concentrations were reached between 40 and 60 min (16.5±2.1 μg/ml in 40 min and 16.6±2.0 in 60 min, respectively) with the concentration being relatively constant during this period. There was no significant effect on the plasma concentration of thiobarbituric acid reactive substances (TBARS) during the administration of K203, indicating an absence of oxidative stress. Indeed, administration of K203 led to a significant increase in low molecular weight antioxidants which could tentatively be interpreted as representing a beneficial effect.

• MeSH
• antioxidancia farmakokinetika   terapeutické užití   MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• krevní plazma chemie   MeSH
• organofosfáty antagonisté a inhibitory   MeSH
• oxidační stres účinky léků   MeSH
• oximy farmakokinetika   terapeutické užití   MeSH
• potkani Wistar MeSH
• reaktivátory cholinesterázy farmakokinetika   terapeutické užití   MeSH
• statistika jako téma MeSH
• vysokoúčinná kapalinová chromatografie metody   využití   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH